integrated traditional and western medicine for treatment of depression based on syndrome...

JTCM |www. journaltcm. com March 15, 2012 | volume 32 | Issue 1 |

Online Submissions: http://www.journaltcm.com J Traditional Chinese Medicine 2012 March 15; 32(1): [email protected] ISSN 0255-2922

© 2012 JTCM. All rights reserved.

Evidence-based Study

KOU Mei-jing, CHEN Jia-xu, School of Pre-clinical Medi-cine, Beijing University of Chinese Medicine, Beijing 100029,China; Hubei University of Chinese Medicine, Hubei 430061,ChinaCorrespondence to: CHEN Jia-Xu, School of Pre-clinicalMedicine, Beijing University of Chinese Medicine, ChaoyangDistrict, Beijing 100029, PChina. [email protected]: +86-10-64286656Accepted: July 15, 2011

AbstractOBJECTIVE: To systematically review the benefitsof integrated traditional and Western medicinetherapies based on the Hamilton depression scale(HAMD) following syndrome differentiation of de-pression.

METHODS: We searched six English and Chineseelectronic databases for randomized clinical trials(RCTs) on integrated traditional and Western medi-cine for treatment of depression. Two authors ex-tracted data and independently assessed the trialquality. RevMan 5 software was used for data analy-ses with an effect estimate presented as weightedmean difference (WMD) with a 95% confidence in-terval (CI).

RESULTS: Seven RCTs with 576 participants wereidentified for this review. All trials were eligible forthe meta-analysis and were evaluated as unclear orhaving a risk of bias. Meta-analysis showed, com-pared with Western medicine alone, integrated tra-ditional and Western medicine based on syndromedifferentiation could improve the effect of treat-ment represented by the HAMD [WMD=-2.39, CI

(-2.96,-1.83), Z=8.29, P<0.00001]. There were no re-ported serious adverse effects that were related tointegrated traditional and Western medicine basedtherapies in these trials.

CONCLUSIONS: Integrated traditional and Westernmedicine based therapies for the syndrome differ-entiation of depression significantly improved theHAMD, illustrating that combining therapies fromintegrated traditional and Western medicine fortreatment of depression is better than Westernmedicine alone. However, further large, rigorouslydesigned trials are warranted due to the insuffi-cient methodological rigor seen in the trials includ-ed in this study.

© 2012 JTCM. All rights reserved.

Key words: Syndrome differentiation; Depression;Integrated traditional and western medicine; Me-ta-analysis; Randomized controlled trials

INTRODUCTIONDepression is a form of mood disorder, where sufferersexperience psychological and somatic symptoms[1]. Inci-dence of depression has significantly increased in re-cent years, becoming a direct threat to the health of theyoung and elderly. Currently, drug therapy is the maintreatment of this disease. The efficacy of these drugshas been proven, but drug dependence and side effectsare a real risk when using these medications.In traditional Chinese medicine (TCM), depression iscategorized as depressive psychosis or depressive dis-ease. Currently, TCM combined with Western medi-cine has been widely used as a treatment of depressionin China. Thousands of clinical studies, ranging from

Integrated traditional and Western medicine for treatment of de-pression based on syndrome differentiation: a meta-analysis of ran-domized controlled trials based on the Hamilton depression scale

KOU Mei-jing寇美静, CHEN Jia-xu陈家旭aa

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JTCM | www. journaltcm. com March 15, 2012 | volume 32 | Issue 1 |

Kou MJ et al. Integrative medicine upon syndrome differentiation for depression: a meta-analysis

case reports and case series, to controlled and random-ized trials, have reported the effectiveness of TCM fordepression, but the conclusions from these trials arenot consistent. Limited sample size is one of the maincauses behind this ambiguity. The present meta-analy-sis of randomized controlled trials using the Hamiltondepression scale (HAMD) as a measure of outcome,aims to evaluate the evidence for the effectiveness of us-ing integrated traditional and Western based medicineon syndrome differentiation for the treatment of de-pression.

METHODSSearch strategyLiterature searches were conducted on the China Na-tional Knowledge Infrastructure (1999 – 2010), theVIP Database for Chinese Technical Periodicals (1999–2010), the Chinese Biomedical Literature Database(1999–2010), PubMed (1999–2010), Embase (fromits inception until 2009), and the Cochrane Library (Is-sue 3, 2009). The reference lists in the retrieved paperswere then browsed. All searches were accomplished bythe end of March 2010. Search terms including "de-pression", "TCM", "Integrated traditional and Westernmedicine", "TCM combined with Western medicine","syndrome differentiation", and "clinical trial" wereused in various combinations, depending on the data-base searched. The bibliographies of included trialswere searched for additional references.

Inclusion criteriaWe included randomized clinical trials (RCTs) compar-ing integrated traditional and Western medicine versusWestern medicine alone. All selected trials chose treat-ment based on syndrome differentiation. RCTs werethe only study design chosen to minimize any poten-tial bias where nonobjective or patient-reported out-comes were used. When more than one publication de-scribed a single study, we extracted data from the oneproviding the most detailed information. Non-RCT tri-als were excluded.

Assessment of methodological qualityThe methodological quality of trials was assessed by ex-amining: the generation of allocation sequence; the al-location concealment; baseline characteristics; blind-ing; and withdrawals/dropouts. Based on the "Risk ofBias" assessment tool on the Cochrane Handbook forSystematic Reviews of Interventions[2], quality of the in-cluded trials was categorized as "low risk of bias","high risk of bias", and "uncertain risk of bias".

Data extractionThe following study characteristics were tabulated

from the trials: design, participants and diagnosis, inter-vention and comparator, and clinical outcomes.

Statistical analysesThe statistical package, RevMan 4.3.2, which was pro-vided by the Cochrane Collaboration, was used for da-ta analyses. Due to sufficient similarity between thestudies, data outcomes were measured as weightedmean difference (WMD), with 95% confidence inter-val (CI).

RESULTSDescription of included trialsIn this review, 612 articles were selected from electron-ic and manual searches. Only 7 articles met the inclu-sion criteria[3-9]. All studies were journal articles andpublished between 2001-2009. The exclusion criteriawere: 1) repeat clinical trials; 2) non-randomized con-trolled trial[10,13]; 3) therapy not based on TCM syn-drome differentiation[11,14,15,17,20]; 4) interventions notmeeting the inclusion criteria; and 5) the HAMD scorenot used in the study[12,16].

Test characteristicsDiagnostic criteria: Altogether, 576 cases were includedin this study. Five trials used the Chinese Classificationand Diagnostic Criteria of Mental Disorders Version 3(CCMD-3) [3,6-9], one trial used the Chinese Classifica-tion and Diagnostic Criteria of Mental Disorders Ver-sion 2 (CCMD-2)[5], and one trial failed to identify thesource of diagnostic criteria[4]. After reading this article,it was found to meet the clinical diagnostic criteria.Treatment programs: Two groups were included in allarticles, the treatment group and the control group. Pa-tients in the control groups only received Western med-ical treatment, while those in the treatment groups re-ceived treatment from Western medicine and Chineseherbs which were prescribed following a doctor's indi-cation of syndrome differentiation. Eleven syndromesand 12 Chinese herbal decoctions were described inthis study (shown in Table 1).Outcome indicators: All seven studies used theHAMD (shown in Table 2).

Methodological quality of included trialsAll 7 trials were described as randomized, but only onetrial gave details of the methods used for generating theallocation sequence (i.e. random number tables). Giv-en these findings, we evaluated that the randomizationquality in one trial was adequate. The quality of the re-maining trials was unclear.All trials reported that baseline characteristics betweenthe groups were comparable. No trials clearly described

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the method used to generate allocation concealment.No trials mentioned who was blinded to treatment allo-cation. Only one trial reported withdrawal/dropout in-formation. No trial provided information on inten-tion-to-treat, or prior sample size estimation. Accord-ingly, the included trials had generally low methodolog-ical quality (with high risk of bias), and most of thestudies fell into the uncertain risk of bias category(shown in Table 3).

Meta-analysis of Hamilton Depression Scale scoresThe outcome of meta-analysis shows there is significantdifference between treatment group and control group.WMD=-2.39, CI (-2.96,-1.83), Z=8.29, P<0.00001(shown in Figure 1).

DISCUSSIONSyndrome differentiation is one of the basic characteris-tics of TCM theory. Based on syndrome differentia-

tion, a disease may have different types of syndromes.Therefore, a variety of therapies in TCM may exist, ac-cording to the patient's condition, for the treatment ofthe same disease[12]. In this study, we found 11 syn-dromes involved in depression, including the syn-drome of blood stasis due to deficient Qi, the syn-drome of stagnation of liver Qi and spleen deficiency,the syndrome of stagnation of liver Qi, the syndromeof stagnation of liver Qi and endogenous heat due toyin deficiency, the syndrome of deficiency of bothheart and spleen, the syndrome of disharmony betweenheart and kidney, the syndrome of stagnated liver Qiand disturbing phlegm, the syndrome of Qi depressiontransforming into fire, Qi stagnation and blood stasis,the syndrome of yin deficiency of liver and kidney, andthe syndrome of kidney deficiency and stagnation ofliver Qi. The most common syndrome seen in thisstudy was the syndrome of stagnation of liver Qi andspleen.

Table 1 Syndromes and treatments found in the included trials

Included trials

Shaojing3

Lihong4

Jiangyouqian5

Niusuying6

Zhangtao7

Qihaojun8

Liujinpeng9

Treatment groupDecoction benefiting Qi and relieving Qi stagnation with modification for syndrome ofblood stasis due to deficient Qi, combined with DeanxitXiaoyao powder for syndrome of stagnation of liver Qi and spleen deficiency,combined with fluoxetine hydrochloride

Decoction of danzhi xiaoyao for syndrome of stagnation of liver Qi, decoction ofHuanglian Wendan for syndrome of stagnation of liver Qi and endogenous heat due toyin deficiency, Guipi decoction for syndrome of deficiency of both heart and spleen,Liuwei dihuang pill and Jiaotai pill for syndrome of disharmony between heart andkidney, combined with fluoxetine

Chaihu shugan powder for syndrome of stagnated liver Qi and disturbing phlegm,decoction of Danzhi Xiaoyao for syndrome of Qi depression transforming into fire,Xuefu zhuyu decoction for syndrome of Qi stagnation and blood stasis, oral liquid ofZishui Qinggan for syndrome of yin deficiency of liver and kidney, Yueju pill forsyndrome of stagnation of liver Qi and spleen deficiency, combined with paroxetine

Xiaoyao powder for syndrome of stagnation of liver Qi and spleen deficiency, Xiaoyaopowder and Guipi decoction for syndrome of deficiency of both heart and spleen,Xiaoyao powder and Liuwei Dihuang pill for syndrome of yin deficiency of liver andkidney, combined with Seroxat

Decoction of Bushen Jieyu for syndrome of kidney deficiency and stagnation of liver Qi,combined with fluoxetine

Chaihu shugan powder for syndrome of stagnated liver Qi, Xuefu zhuyu decoction forsyndrome of Qi stagnation and blood stasis, Wendan decoction for syndrome ofstagnated liver Qi and disturbing phlegm, Guipi decoction for syndrome of deficiency ofboth heart and spleen, combined with venlafaxine

Control group

Deanxit

Fluoxetine hydrochloride

Fluoxetine

Paroxetine

Seroxat

Fluoxetine

Venlafaxine

Table 2 Hamilton depression scale score from included trials

Included trials

Shaojing3

Lihong4

Jiangyouqian5

Niusuying6

Zhangtao7

Treatment group

cases

2841305060

Before treatment

28.83±4.9630.80±3.8019.50±3.4237.75±5.5132.06±6.91

After treatment

17.97±4.079.70±1.808.90±4.8013.12±2.1412.02±5.86

Control group

cases

2839305040

Before treatment

28.17±5.1330.90±3.7020.37±3.4736.71±5.5931.63±7.86

After treatment

18.53±4.1311.50±2.1011.90±4.7116.33±4.3715.36±6.08

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Qihaojun8

Liujinpeng9

6030

25.31±6.0527.06±4.85

10.51±2.355.10±9.32

6030

25.41±5.0826.35±4.65

13.81±4.496.04±8.68

Table 3 Methodological quality of included trials

Included trials

Shaojing3

Lihong4

Jiangyouqian5

Niusuying6

Zhangtao7

Qihaojun8

Liujinpeng9

Treatmentduration(w)

6668666

outcomeindicatorHAMDHAMDHAMDHAMDHAMDHAMDHAMD

Random

unclearunclearunclear

random number tablesunclearunclearunclear

Allocationconcealment

unclearunclearunclearunclearunclearunclearunclear

Blind

unclearunclearunclearunclearunclearunclearunclear

Baseline

ConsistentConsistentConsistentConsistentConsistentConsistentConsistent

withdrawals/dropouts

0200000

Figure 1 Meta-analysis of Hamilton depression scale scores.

Syndrome of stagnation of liver Qi and spleen deficien-cy is one of the common syndromes of depression. Ex-cessive pressure from work or a poor emotional statewill lead to the dysfunction of "liver controlling con-veyance and dispersion" and the stagnation of liver Qiwill result in spleen and stomach disorders. As a result,depression, anxiety, fatigue and other symptoms willoccur. Therefore, further research between depressionand stagnation of liver Qi and spleen deficiency shouldbe conducted.HAMD is a classic depression rating scale, which ismost commonly used in clinical assessment of depres-sion. It is also an objective scale to evaluate effective-ness of treatment. The meta-analysis on data from theHAMD showed a significant benefit of integrated tra-ditional and Western medicine based on syndrome dif-ferentiation in the treatment of depression. Thoughthe quality of all the included trials is generally low, theconclusions from a meta-analysis are more comprehen-sive and reliable than a single trail.Based on the "risk of bias" assessment tool in the Co-chrane approach, the quality of most included trialswas categorized as "uncertain risk of bias". Proper ran-domization techniques need to be used, clearly de-scribed, and fully reported. An intention-to-treat prin-ciple and an appropriate method for including drop-outs in data analyses are also important in the design ofthe trials. Considering there are insufficient high-quali-

ty trials on integrated traditional and Western medi-cine based on syndrome differentiation treatment of de-pression, proof of the effectiveness of this mode oftreatment will require further rigorous trials. There-fore, the authors suggest that the efficacy of TCMshould be seriously evaluated according to the princi-ples of evidence-based medicine and based on syn-drome differentiation, even though abundant clinicalexperience, especially case reports, have been repeatedand treatments have lasted for thousands of years[19-21].

AcknowledgmentsThis work was supported by the National Natural Sci-ence Foundation of China (81072756, 30672578), theChinese National Funds for Distinguished Young Sci-entists (30825046), the Hi-Tech Research and Devel-opment Program of China (2008AA02Z406), and theProgram for Innovative Research Teams in Beijing Uni-versity of Chinese Medicine (2011CXTD-07).

Disclosure StatementNo competing financial interests exist.

REFERENCES1 Paykel E. Basic concepts of depression. Dialogues Clin

Neurosci 2008; 10: 279-2892 Higgins JPT, Green S. Cochrane Handbook for Systemat-

ic Reviews of Interventions Version 5.0.2 [updated Sep-tember 2009]. The Cochrane Collaboration 2009; Avail-

4



able from www. cochrane-handbook. Org3 Shao J, Liu YG. Effects of benefiting qi and relieving qi

stagnation decoction on elderly depression with syndromeof blood stasis due to deficient qi. Clin J Tradit Chin Med2008; 20: 588-589

4 Li H, Xu S, Li B. 41 cases depression with syndrome ofstagnation of liver qi and spleen deficiency treated withXiaoyao powder and Deanxit. Shaanxi Tradit Chin Med2009; 30: 49-50

5 Jiang YQ. 30 cases depression treated with integrated tra-ditional and western medicine based on syndrome differen-tiation. Liaoning J Tradit Chin Med 2001; 28: 236

6 Niu SY, Li N, You H. Effects of Integrated traditional andwestern medicine based on syndrome differentiation on de-pression. Chin J Clin Rehabil, 2006; 10: 7-9

7 Zhang T, Shao P, Chen M. 60 cases depression treatedwith Chinese herbs based on syndrome differentiationcombined with western medicine. Clin J Tradit Chin Med2004; 16: 554-555

8 Qi HJ. 60 cases old depression treated with integrated tra-ditional and western medicine. J Tradit Chin Med 2009;50: 327-328

9 Liu JP, Meng L, Zhang XP. Clinical control study of re-fractory depression treated with integrated traditional andwestern medicine. Gansu Coll Tradit Chin Med 2009; 26:21-23

10 Kong L, Yan H. Clinical observation on the effect of Jieyumixture combined with Fluoxetine for 50 depression pa-tients. J Tradit Chin Med 2009; 50: 699-700

11 Pang JM, Liao JG, Zhang WM. Clinical observation ofintegrative Chinese and western medicine on treatment ofpost-stroke depression. World J Integr Tradit West Med2009; 4: 499-501

12 Zhou B, Zeng QQ, Peng ZC, Zhou ZG, Wang GX.Grain of Yishenshugan in Treating 30 cases of depressionafter stroke. Shaanxi J Tradit Chin Med 2009; 30: 520-521

13 Shen JL. Jieyu Chaihushugan decoction with deanxit intreatment of 30 cases of post-stroke depression. J Pract Tra-dit Chin Med 2009; 25: 392-393

14 Hao JX, Pu YX, Dang XS. Chinese and western medicinecombined in treatment of depression. Guide Chin Med2009; 7: 135-136

15 Tang QS, Qu M. Integrative medicine in depression.Chin J Integr Tradit West Med 2009; 29: 283-288

16 Yang L, Rong PH. Xiaoyaosan combined with Fluoxetinein treatment of 30 cases of depression after stroke. ShaanxiJ Tradit Chin Med 2009; 30: 150-151

17 Li QY, Wang XH, Song RH, Zhang SR, Song DY, KongLZ. Control study on menopausal depression treated withintegrated Chinese and western medicine. World ChinMed 2009; 4: 80-81

18 Sun XY, Chen AQ, Xu XF, Zhang HG, Tang QS, ZhangHY. Randomized, double blind, placebo controlled trial ofShuganjieyu capsule in the treatment of mild or moderatedepression. Chin J New Drug 2009: 413-416, 457

19 Zhao H, Wan X, Chen JX. A mini review of traditionalChinese medicine for the treatment of depression in Chi-na. Am J Chin Med 2009; 37: 207-213

20 Chen JX, Wang LM, Tang YT. The enlightenment of evi-dence-based medicine on traditional Chinese medical clini-cal practice. J Beijing Univ Tradit Chin Med 2001; 24:7-10

21 Chen JX, Hu LS. Traditional Chinese medicine for thetreatment of chronic prostatitis in China: a systematic re-view and mata-analysis. J Altern Complement Med 2006;12: 763-769

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